Human and rat natural killer (NK) cells and K cells mediating antibody-dependent cellular cytotoxicity have been shown to be large granular lymphocytes (LGL). The majority of LGL formed conjugates with, and caused lysis of, NK-susceptible target cells. The specificity of human NK cells was examined by selective monolayer adsorptions and evidence for multiple antigens, recognized by subsets of NK cells, was obtained. Interferon caused direct augmentation of NK and K cell activities of LGL, with the predominant mechanism being an increase in lytic efficiency. Studies on mechanisms for depressed NK activity have shown: suppressor cells in normal SJL mice; patients with Chediak-Higashi syndrome to have a marked, selective deficit in NK and K cell activities; and the carcinogen, urethane, and the tumor promotor, phorbol ester, to be able to depress NK activity. In short-term in vivo assays, NK cells played a major role in resistance to tumor challenge. Granulocytes of normal human donors have substantial cytostatic activity against cultured cell lines and this activity was depressed in most tumor-bearing patients, apparently due to circulating inhibitory factors. Lymphoproliferative response of breast cancer patients to autologous tumor antigen was shown to be a significant prognostic factor, with lack of activity predictive of disease recurrence.